Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study

Paula Simplício da Silva, Mauro Felippe Felix Mediano, Gilberto Marcelo Sperandio da Silva, Patricia Dias de Brito, Claudia Santos de Aguiar Cardoso, Cristiane Fonseca de Almeida, Luiz Henrique Conde Sangenis, Roberta Olmo Pinheiro, Alejandro Marcel Hasslocher-Moreno, Pedro Emmanuel Alvarenga Americano do Brasil, Andrea Silvestre de Sousa, Paula Simplício da Silva, Mauro Felippe Felix Mediano, Gilberto Marcelo Sperandio da Silva, Patricia Dias de Brito, Claudia Santos de Aguiar Cardoso, Cristiane Fonseca de Almeida, Luiz Henrique Conde Sangenis, Roberta Olmo Pinheiro, Alejandro Marcel Hasslocher-Moreno, Pedro Emmanuel Alvarenga Americano do Brasil, Andrea Silvestre de Sousa

Abstract

Background: Several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. Although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in Chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. We investigated the effects of omega-3 PUFAs on markers of inflammation and lipid profile in chronic Chagas cardiomyopathy patients.

Methods: The present study was a single-center double-blind clinical trial including patients with chronic Chagas cardiomyopathy. Patients were randomly assigned to receive omega-3 PUFAs capsules (1.8g EPA and 1.2g DHA) or placebo (corn oil) during an 8-week period. Cytokines, fasting glucose, lipid, and anthropometric profiles were evaluated.

Results: Forty-two patients (23 women and 19 men) were included in the study and there were only two losses to follow-up during the 8-week period. Most of sociodemographic and clinical characteristics were similar between the groups at baseline, except for the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17α, and IFNγ. The omega-3 PUFAs group demonstrated greater improvements in serum triglycerides (-21.1 vs. -4.1; p = 0.05) and IL-10 levels (-10.6 vs. -35.7; p = 0.01) in comparison to controls after 8 weeks of intervention. No further differences were observed between groups.

Conclusion: Omega-3 PUFAs supplementation may favorably affect lipid and inflammatory profile in chronic Chagas cardiomyopathy patients, demonstrated by a decrease in triglycerides and improvements on IL-10 concentration. Further studies examining the clinical effects of omega-3 fatty acids supplementation in chronic Chagas cardiomyopathy are necessary.

Trial registration: NCT01863576.

Keywords: Chagas cardiomyopathy; Chagas disease; Cytokines; Lipid profile; Omega-3.

Figures

Fig. 1
Fig. 1
Progress of participants through the trial

References

    1. Rassi A, Jr, Rassi A, Marcondes de Rezende J. American Trypanosomiasis (Chagas Disease) Infect Dis Clin North Am. 2012;26:275–91. doi: 10.1016/j.idc.2012.03.002.
    1. WHO | Chagas disease (American trypanosomiasis) [Internet]. WHO. [cited 2017 Feb 19]. Available from:
    1. Coura JR, Viñas PA. Chagas disease: a new worldwide challenge. Nature. 2010;465:S6–7. doi: 10.1038/nature09221.
    1. Marin Neto JA, Simões MV, Sarabanda AV. Chagas’ heart disease. Arq Bras Cardiol. 1999;72:247–80. doi: 10.1590/S0066-782X1999000300001.
    1. Rocha MOC, Ribeiro ALP, Teixeira MM. Clinical management of chronic Chagas cardiomyopathy. Front Biosci J Virtual Libr. 2003;8:e44–54. doi: 10.2741/926.
    1. Rassi A, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375:1388–402. doi: 10.1016/S0140-6736(10)60061-X.
    1. Punukollu G, Gowda RM, Khan IA, Navarro VS, Vasavada BC. Clinical aspects of the Chagas’ heart disease. Int J Cardiol. 2007;115:279–83. doi: 10.1016/j.ijcard.2006.03.004.
    1. Ribeiro AL, Nunes MP, Teixeira MM, Rocha MOC. Diagnosis and management of Chagas disease and cardiomyopathy. Nat Rev Cardiol. 2012;9:576–89. doi: 10.1038/nrcardio.2012.109.
    1. Cunha-Neto E, Chevillard C. Chagas Disease Cardiomyopathy: Immunopathology and Genetics. Mediators Inflamm. 2014;2014:e683230. doi: 10.1155/2014/683230.
    1. Pereira IR, Vilar-Pereira G, da Silva AA, Lannes-Vieira J. Severity of chronic experimental Chagas’ heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease. Mem Inst Oswaldo Cruz. 2014;109:289–98. doi: 10.1590/0074-0276140033.
    1. Chaves AT, de Assis Silva Gomes Estanislau J, Fiuza JA, Carvalho AT, Ferreira KS, Fares RCG, et al. Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses. BMC Infect Dis. 2016;16:191. doi: 10.1186/s12879-016-1523-1.
    1. Sousa GR, Gomes JAS, Fares RCG, de Damásio MP S, Chaves AT, Ferreira KS, et al. Plasma Cytokine Expression Is Associated with Cardiac Morbidity in Chagas Disease. PLoS One. 2014;9:e87082. doi: 10.1371/journal.pone.0087082.
    1. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1223–30. doi: 10.1016/S0140-6736(08)61239-8.
    1. Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011;57:870–9. doi: 10.1016/j.jacc.2010.11.017.
    1. Backes J, Anzalone D, Hilleman D, Catini J. The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis. 2016;15:118. doi: 10.1186/s12944-016-0286-4.
    1. Blondeau N. The nutraceutical potential of omega-3 alpha-linolenic acid in reducing the consequences of stroke. Biochimie. 2016;120:49–55. doi: 10.1016/j.biochi.2015.06.005.
    1. Endo J, Arita M. Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. J Cardiol. 2016;67:22–7. doi: 10.1016/j.jjcc.2015.08.002.
    1. Chrysohoou C, Metallinos G, Georgiopoulos G, Mendrinos D, Papanikolaou A, Magkas N, et al. Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial. Vascul Pharmacol. 2016;79:43–50. doi: 10.1016/j.vph.2016.01.005.
    1. Silva PS, da Silva GM S, de Souza AP, Cardoso CSA, Fonseca CA, Brito PD, et al. Effects of omega-3 polyunsaturated fatty acid supplementation in patients with chronic chagasic cardiomyopathy: study protocol for a randomized controlled trial. Trials. 2013;14:379. doi: 10.1186/1745-6215-14-379.
    1. Dias JCP, Ramos AN, Gontijo ED, Luquetti A, Shikanai-Yasuda MA, Coura JR, et al. 2 nd Brazilian Consensus on Chagas Disease, 2015. Rev Soc Bras Med Trop. 2016;49Suppl 1:3–60. doi: 10.1590/0037-8682-0505-2016.
    1. Slater B, Marchioni DL, Fisberg RM. Estimating prevalence of inadequate nutrient intake. Rev Saude Publica. 2004;38:599–605. doi: 10.1590/S0034-89102004000400019.
    1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1-253.
    1. Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status. Am J Clin Nutr. 1981;34:2540–5.
    1. Frisancho AR. Anthropometric standards for the assessment of growth and nutritional status. University of Michigan. 1990.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.
    1. Salvador MB, Sarkis KS, Silva RG, de Zerbini CA F, Martini LA. Avaliação da ingestão de ácidos graxos, antioxidantes e da composição corporal em mulheres com artrite reumatóide; Fatty acids, antioxidants and body composition evaluation in woman with reumathoid arthritis. Nutr Rev Soc Bras Aliment Nutr. 2008;33:17–30.
    1. Kew S, Mesa MD, Tricon S, Buckley R, Minihane AM, Yaqoob P. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr. 2004;79:674–81.
    1. Mozaffarian D, Bryson CL, Lemaitre RN, Burke GL, Siscovick DS. Fish Intake and Risk of Incident Heart Failure. J Am Coll Cardiol. 2005;45:2015–21. doi: 10.1016/j.jacc.2005.03.038.
    1. Tajuddin N, Shaikh A, Hassan A. Prescription omega-3 fatty acid products: considerations for patients with diabetes mellitus. Diabetes Metab Syndr Obes Targets Ther. 2016;9:109–18.
    1. Mozaffarian D, Lemaitre RN, King IB, Song X, Spiegelman D, Sacks FM, et al. Circulating Long-Chain ω-3 Fatty Acids and Incidence of Congestive Heart Failure in Older Adults: The Cardiovascular Health Study: A Cohort Study. Ann Intern Med. 2011;155:160. doi: 10.7326/0003-4819-155-3-201108020-00006.
    1. Perini JÂDL, Stevanato FB, Sargi SC, Visentainer JEL, Dalalio MMDO, Matshushita M, et al. Omega-3 and omega-6 polyunsaturated fatty acids: metabolism in mammals and immune response. Rev Nutr. 2010;23:1075–86. doi: 10.1590/S1415-52732010000600013.
    1. Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol. 2006;48:677–85. doi: 10.1016/j.jacc.2006.03.052.
    1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239. doi: 10.1016/j.jacc.2013.05.019.
    1. Gastelurrutia P, Lupón J, de Antonio M, Urrutia A, Díez C, Coll R, et al. Statins in heart failure: the paradox between large randomized clinical trials and real life. Mayo Clin Proc. 2012;87:555–60. doi: 10.1016/j.mayocp.2012.02.018.
    1. Kastelein JJP, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014;8:94–106. doi: 10.1016/j.jacl.2013.10.003.
    1. Tousoulis D, Plastiras A, Siasos G, Oikonomou E, Verveniotis A, Kokkou E, et al. Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome. Atherosclerosis. 2014;232:10–6. doi: 10.1016/j.atherosclerosis.2013.10.014.
    1. von Schacky C. n-3 PUFA in CVD: influence of cytokine polymorphism. Proc. Nutr Soc. 2007;66:166–70. doi: 10.1017/S0029665107005411.
    1. Zhao YT, Shao L, Teng LL, Hu B, Luo Y, Yu X, et al. Effects of n-3 polyunsaturated fatty acid therapy on plasma inflammatory markers and N-terminal pro-brain natriuretic peptide in elderly patients with chronic heart failure. J Int Med Res. 2009;37:1831–41. doi: 10.1177/147323000903700619.
    1. Xin W, Wei W, Li X. Effects of fish oil supplementation on inflammatory markers in chronic heart failure: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2012;12:77. doi: 10.1186/1471-2261-12-77.
    1. Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, et al. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr. 2011;141:207–13. doi: 10.3945/jn.110.130021.
    1. Satoh-Asahara N, Shimatsu A, Sasaki Y, Nakaoka H, Himeno A, Tochiya M, et al. Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia. Diabetes Care. 2012;35:2631–9. doi: 10.2337/dc12-0269.
    1. Gharekhani A, Khatami M-R, Dashti-Khavidaki S, Razeghi E, Abdollahi A, Hashemi-Nazari S-S, et al. Effects of Oral Supplementation With Omega-3 Fatty Acids on Nutritional State and Inflammatory Markers in Maintenance Hemodialysis Patients. J Ren Nutr. 2014;24:177–85. doi: 10.1053/j.jrn.2014.01.014.
    1. da Silva EL. Omega-3 Fatty Acids Improve Lipid Metabolism and Inflammatory Markers in Patients with Heart Failure Undergoing Exercise Training. Ommega Int. 2015;2:1–8.
    1. Darghosian L, Free M, Li J, Gebretsadik T, Bian A, Shintani A, et al. Effect of Omega-Three Polyunsaturated Fatty Acids on Inflammation, Oxidative Stress, and Recurrence of Atrial Fibrillation. Am J Cardiol. 2015;115:196–201. doi: 10.1016/j.amjcard.2014.10.022.
    1. Vitelli-Avelar DM, Sathler-Avelar R, Teixeira-Carvalho A, Pinto Dias JC, Gontijo ED, Faria AM, et al. Strategy to assess the overall cytokine profile of circulating leukocytes and its association with distinct clinical forms of human Chagas disease. Scand J Immunol. 2008;68:516–25. doi: 10.1111/j.1365-3083.2008.02167.x.
    1. Guedes PMM, Gutierrez FRS, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM, et al. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas’ disease. PLoS Negl Trop Dis. 2012;6:e1630. doi: 10.1371/journal.pntd.0001630.
    1. Rocha Rodrigues DB, Dos Reis MA, Romano A, de Pereira SA L, de PA TV, Tostes SJ, et al. In situ expression of regulatory cytokines by heart inflammatory cells in Chagas’ disease patients with heart failure. Clin Dev Immunol. 2012;2012:361730.
    1. Akl EA, Briel M, You JJ, Sun X, Johnston BC, Busse JW, et al. Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review. BMJ. 2012;344:e2809. doi: 10.1136/bmj.e2809.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi